This proposal aims to elucidate mechanisms of environmental enrichment (EE)-induced recovery from perinatal hypoxia. Brain damage induced by premature birth causes chronic neurodevelopmental impairments such as intellectual disabilities, locomotor deficits and behavioral disorders. Premature infants are born with an underdeveloped respiratory system, exposing them to hypoxic conditions during a critical developmental period of neuronal maturation, synapse formation, and extensive gliogenesis. This oxygenation failure predisposes preterm infants to dysmaturation of cerebral white and gray matter. The divergent neurodevelopmental timeline of rodents and humans allows for a postnatal rodent hypoxia paradigm that models human preterm birth. One intervention that enhances recovery in this model is housing animals in EE. By simply increasing levels of cognitive, physical, and social stimulation, mice exposed to perinatal hypoxia recover normal cortical interneuron maturation and subcortical white matter myelination, restore spatial memory, and improve locomotor coordination. These findings support the overarching hypothesis that EE promotes recovery after perinatal hypoxia by enhancing neuronal and glial maturation. However, it is unknown whether EE affects cortical pyramidal neurons and their interhemispheric commissural axons, which are essential for complex cognitive behaviors, learning, and coordinated movement. To determine if EE rescues cortical pyramidal neuron maturation following perinatal hypoxia, morphological and electrophysiological properties will be examined. Then, colossal axon myelination and conduction velocity will be assessed to determine if EE rescues callosal axon function following perinatal hypoxia. Finally, changes in oligodendrocyte mRNA translation will be examined to determine if EE restores translation of oligodendrocyte genes involved in metabolic support of axons. This study will provide crucial insight into the mechanisms of EE-induced recovery from perinatal hypoxia, and aid in the development of more targeted and effective treatment options for preterm infants.